Amazing Science

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, researchers conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans).

Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, they identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and they show elevated gut CXCL5 transcript expression in patients with UC.

These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.

Humans inherited genetic material from Neanderthals that affects the shape of our noses, finds a new study led by UCL researchers.

Scientists have made groundbreaking progress in characterizing the fraction of human DNA that varies between individuals.

For more than 20 years, scientists have relied on the human reference genome, a consensus genetic sequence, as a standard against which to compare other genetic data. Used in countless studies, the reference genome has made it possible to identify genes implicated in specific diseases and trace the evolution of human traits, among other things. But it has always been a flawed tool. One of its biggest problems is that about 70 percent of its data came from a single man of predominantly African-European background whose DNA was sequenced during the Human Genome Project, the first effort to capture all of a person's DNA. As a result, it can tell us little about the 0.2 to one percent of genetic sequence that makes each of the seven billion people on this planet different from each other, creating an inherent bias in biomedical data believed to be responsible for some of the health disparities affecting patients today. Many genetic variants found in non-European populations, for instance, aren't represented in the reference genome at all.

For years, researchers have called for a resource more inclusive of human diversity with which to diagnose diseases and guide medical treatments. Now scientists with the Human Pangenome Reference Consortium have made groundbreaking progress in characterizing the fraction of human DNA that varies between individuals. As they recently published in Nature, they have assembled genomic sequences of 47 people from around the world into a so-called pangenome in which more than 99 percent of each sequence is rendered with high accuracy. Layered upon each other, these sequences revealed nearly 120 million DNA base pairs that were previously unseen. While it's still a work in progress, the pangenome is public and can be used by scientists around the world as a new standard human genome reference, says The Rockefeller University's Erich D. Jarvis, one of the primary investigators.

"This complex genomic collection represents significantly more accurate human genetic diversity than has ever been captured before," he says. "With a greater breadth and depth of genetic data at their disposal, and greater quality of genome assemblies, researchers can refine their understanding of the link between genes and disease traits, and accelerate clinical research."

Sourcing diversity

Cat genes reveal how invention of agriculture bonded cats with people in ancient Mesopotamia, leading to worldwide feline migration with humans.

Nearly 10,000 years ago, humans settling in the Fertile Crescent, the areas of the Middle East surrounding the Tigris and Euphrates rivers, made the first switch from hunter-gatherers to farmers. They developed close bonds with the rodent-eating cats that conveniently served as ancient pest-control in society's first civilizations.

A new study at the University of Missouri found this lifestyle transition for humans was the catalyst that sparked the world's first domestication of cats, and as humans began to travel the world, they brought their new feline friends along with them. Leslie A. Lyons, a feline geneticist and Gilbreath-McLorn endowed professor of comparative medicine in the MU College of Veterinary Medicine, collected and analyzed DNA from cats in and around the Fertile Crescent area, as well as throughout Europe, Asia and Africa, comparing nearly 200 different genetic markers. "One of the DNA main markers we studied were microsatellites, which mutate very quickly and give us clues about recent cat populations and breed developments over the past few hundred years," Lyons said. "Another key DNA marker we examined were single nucleotide polymorphisms, which are single-based changes all throughout the genome that give us clues about their ancient history several thousands of years ago. By studying and comparing both markers, we can start to piece together the evolutionary story of cats."

Lyons added that while horses and cattle have seen various domestication events caused by humans in different parts of the world at various times, her analysis of feline genetics in the study strongly supports the theory that cats were likely first domesticated only in the Fertile Crescent before migrating with humans all over the world. After feline genes are passed down to kittens throughout generations, the genetic makeup of cats in western Europe, for example, is now far different from cats in southeast Asia, a process known as 'isolation by distance.'

"We can actually refer to cats as semi-domesticated, because if we turned them loose into the wild, they would likely still hunt vermin and be able to survive and mate on their own due to their natural behaviors," Lyons said. "Unlike dogs and other domesticated animals, we haven't really changed the behaviors of cats that much during the domestication process, so cats once again prove to be a special animal."

Lyons, who has researched feline genetics for more than 30 years, said studies like this also support her broader research goal of using cats as a biomedical model to study genetic diseases that impact both cats and people, such as polycystic kidney disease, blindness and dwarfism.

"Comparative genetics and precision medicine play key roles in the 'One Health' concept, which means anything we can do to study the causes of genetic diseases in cats or how to treat their ailments can be useful for one day treating humans with the same diseases," Lyons said. "I am building genetic tools, genetic resources that ultimately help improve cat health. When building these tools, it is important to get a representative sample and understand the genetic diversity of cats worldwide so that our genetic toolbox can be useful to help cats all over the globe, not just in one specific region."

A new high-throughput genomic array offers an unprecedented look into the mouse epigenome, giving researchers an in-depth view into the basis of health and disease in a vital model organism.

The array was developed by scientists at Van Andel Institute, Children's Hospital of Philadelphia and University of Pennsylvania in collaboration with Illumina and FOXO Technologies. It contains more than 296,000 probes that represent the diversity of murine DNA methylation biology.

"DNA methylation is one of the pillars of epigenetics research," said VAI Associate Professor Hui Shen, Ph.D., co-corresponding author of the study that describes the array, which published today in Cell Genomics. "This array gives scientists around the world a powerful new tool to understand the role of methylation in normal processes and in diseases like cancer and many others."

Since the 1980s, it has become clear that epigenetics plays a role in virtually every aspect of health and disease. This revelation has given rise to a growing field that has illuminated vital insights into myriad diseases such as cancer, which is now known to be driven by both genetic and epigenetic errors. The new array includes markers for an extensive list of biological features, including genomic imprinting, aging, cancer, variably methylated regions, germ cell development, tissue specificity, X-linked probes, and epigenetic clocks.

Development of the array was led by Shen, VAI Professor Peter W. Laird, Ph.D., co-corresponding author of the study, and Children's Hospital of Philadelphia and University of Pennsylvania Assistant Professor Wanding Zhou, Ph.D., a former postdoctoral fellow in the Laird and Shen labs. "We learned many lessons from the current and previous generations of human arrays and have improved the overall quality of probe design," said Zhou, who also is a corresponding author of the study. "For example, we optimized the probe selection to cover the diverse biology of DNA methylation in mice while minimizing the chance of probe misuse and artifacts. The array also features probe sets that will enable comparative epigenome analysis between humans and mice as well as among other rodents."

The array allows scientists to interrogate methylation more quickly and more deeply than previous methods. It enabled the team to develop a rich atlas of DNA methylation profiles across more than 1,200 samples, representing diverse cell types, strains and pathologies. Before now, DNA methylation data were available but not centralized. The atlas, made possible by the array, offers scientists a central repository for this critical information. Additionally, the array has been implemented in the popular bioinformatics tool SeSAMe.

Parts of the human genome now available to study for the first time are important for understanding genetic diseases, human diversity, and evolution.

The first truly complete sequence of a human genome, covering each chromosome from end to end with no gaps and unprecedented accuracy, is now accessible through the UCSC Genome Browser and is described in six papers published today (March 31, 2022) in Science.

Since the first working draft of a human genome sequence was assembled at UC Santa Cruz in 2000, genomics research has led to enormous advances in our understanding of human biology and disease. Nevertheless, crucial regions accounting for some 8% of the human genome have remained hidden from scientists for over 20 years due to the limitations of DNA sequencing technologies.

Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, and Adam Phillippy at the National Human Genome Research Institute (NHGRI) organized an international team of scientists—the Telomere-to-Telomere (T2T) Consortium—to fill in the missing pieces. Their efforts have now paid off.

Researchers from the University of Oxford's Big Data Institute have taken a major step towards mapping the entirety of genetic relationships among humans: a single genealogy that traces the ancestry of all of us. The study has been published today in Science.

The past two decades have seen extraordinary advancements in human genetic research, generating genomic data for hundreds of thousands of individuals, including from thousands of prehistoric people. This raises the exciting possibility of tracing the origins of human genetic diversity to produce a complete map of how individuals across the world are related to each other.

Until now, the main challenges to this vision were working out a way to combine genome sequences from many different databases and developing algorithms to handle data of this size. However, a new method published today by researchers from the University of Oxford's Big Data Institute can easily combine data from multiple sources and scale to accommodate millions of genome sequences.

Investigators from UCLA Jonsson Comprehensive Cancer Center have identified a germline biomarker signature that successfully predicts which patients will suffer serious side effects that occur in up to 3 in ten patients on anti-PD1/PDL1 therapy, a promising new approach to treating cancer.

Checkpoint inhibitors that enhance the immune system against PD-1 and PD-L1 show great promise, having substantially improved the prognosis for patients with several advanced cancers, including melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and head and neck cancer.

As promising as they are, these therapies are also associated with a unique set of side effects, called immune-related adverse events (irAEs), believed to be the result of an immune system overstimulated by the therapy. While these side effects are generally treatable, they can in rare cases be very serious, even fatal. In addition, there's currently no way to predict which patients will develop irAEs before starting treatment, requiring clinicians to watch and wait after treatment begins. Notably, the toxicity from checkpoint therapy does not appear to be associated with a patient's cancer or their response to the treatment, supporting the idea that it is a patient-specific reaction.

With a growing need to identify which patients are at risk for irAEs, investigators led by Joanne B. Weidhaas, MD, PhD, MSM, of UCLA Jonsson Comprehensive Cancer Center, vice chair Department of Radiation Oncology, and director Division of Molecular and Cellular Oncology at UCLA Health, examined DNA signatures in 99 patients, looking for patterns that would indicate if inherited DNA biomarkers would predict toxicity. In findings published in Journal for Immunotherapy of Cancer, they report that they were able to identify a biomarker panel that predicts toxicity with 80% accuracy.

"These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly," said Dr. Weidhaas. "While we are still at the early stages of understanding the mechanisms by which these germline mutations regulate immunity and the systemic stress response, our repeated findings that these variant panels can predict systemic toxic responses to cancer therapy are potentially paradigm-shifting."

UK Biobank offers easy access to genomic database for researchers around the world

In the largest single release of whole genomes ever, the UK Biobank (UKBB) this week unveiled to scientists the entire genomes of 200,000 people who are part of a long-term British health study.

The trove of genomes, each linked to anonymized medical information, will allow biomedical scientists to scour the full 3 billion base pairs of human DNA for insights into the interplay of genes and health that could not be gleaned from partial sequences or scans of genome markers. “It is thrilling to see the release of this long-awaited resource,” says Stephen Glatt, a psychiatric geneticist at the State University of New York Upstate Medical University.

Other biobanks have also begun to compile vast numbers of whole genomes, 100,000 or more in some cases (see table, below). But UKBB stands out because it offers easy access to the genomic information, according to some of the more than 20,000 researchers in 90 countries who have signed up to use the data.

“In terms of availability and data quality, [UKBB] surpasses all others,” says physician and statistician Omar Yaxmehen Bello-Chavolla of the National Institute for Geriatrics in Mexico City.

Biobanks

A number of efforts are releasing many thousands of whole genomes, with varying degrees of access, to accelerate biomedical research.

Having enrolled 500,000 middle-age and elderly participants of mostly European ancestry from 2006 to 2010, UKBB is one of the largest genetics research databases in the world. It proved its worth even before releasing whole genomes. Studies of specific DNA markers that vary among participants have revealed hundreds of new disease risk genes. Since 2019 researchers have also been probing participants’ exomes, the 2% of the whole genome sequence (WGS) that encodes proteins; the exomes from nearly all participants became available in the past 2 months. Exome studies are yielding risk genes that are very rare and can’t be found with genotyping data.

But whole genomes will make it possible to explore the influence of noncoding DNA, which controls when genes are turned off or on, and of gene rearrangements, as well as missing, repeated, or extra stretches of DNA in genes. Such changes play a role in diseases such as Huntington disease.

The study, published recently in the journal Nature Neuroscience, is one of the largest genome-wide association studies of its kind ever conducted.

An analysis of data from 1.5 million people has identified 579 locations in the genome associated with a predisposition to different behaviors and disorders related to self-regulation, including addiction and child behavioral problems. With these findings in hand, researchers have constructed a genetic risk score -- a number reflecting a person's overall genetic propensity based on how many risk variants they carry -- that predicts a range of behavioral, medical and social outcomes, including education levels, obesity, opioid use disorder, suicide, HIV infections, criminal convictions and unemployment.

"This study illustrates that genes don't code for a particular disorder or outcome; there are no genes 'for' substance use disorder, or 'for' behavior problems," said joint senior author Danielle Dick, Ph.D., Commonwealth Professor of Psychology and Human and Molecular Genetics at Virginia Commonwealth University. "Instead, genes influence the way our brains are wired, which can make us more at risk for certain outcomes. In this case, we find that there are genes that broadly influence self-control or impulsivity, and that this predisposition then confers risk for a variety of life outcomes."

The study, "Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction," was published today in the journal Nature Neuroscience and was conducted by a consortium of 26 researchers at 17 institutions in the United States and the Netherlands.

It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain.

Neurological disorders such as Parkinson's disease and epilepsy have had some treatment success with deep brain stimulation, but those require surgical device implantation. A multidisciplinary team at Washington University in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn specific types of neurons in the brain on and off and precisely control motor activity without surgical device implantation.

The team, led by Hong Chen, assistant professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology at the School of Medicine, is the first to provide direct evidence showing noninvasive, cell-type-specific activation of neurons in the brain of mammal by combining ultrasound-induced heating effect and genetics, which they have named sonothermogenetics. It is also the first work to show that the ultrasound- genetics combination can robustly control behavior by stimulating a specific target deep in the brain.

Results of the three years of research, which was funded in part by the National Institutes of Health's BRAIN Initiative, were published online in Brain Stimulation May 11, 2021.

The senior research team included experts from both the McKelvey School of Engineering and the School of Medicine, including Jianmin Cui, professor of biomedical engineering; Joseph P. Culver, professor of radiology, of physics and of biomedical engineering; Mark J. Miller, associate professor of medicine in the Division of Infectious Diseases in the Department of Medicine; and Michael Bruchas, formerly of Washington University, now professor of anesthesiology and pharmacology at the University of Washington.

"Our work provided evidence that sonothermogenetics evokes behavioral responses in freely moving mice while targeting a deep brain site," Chen said. "Sonothermogenetics has the potential to transform our approaches for neuroscience research and uncover new methods to understand and treat human brain disorders."

Goldenhar syndrome is a rare congenital disease, affecting early foetal development. This syndrome includes malformations of varying severity, affecting different parts of the face. Its causes and modes of transmission are still poorly understood.

An international collaboration led by the University of Geneva (UNIGE) and Beihang University, in China, has discovered that pathogenic variants of the FOXI3 gene -- responsible for the development of the ear -- cause one form of this developmental disorder. The scientists were also able to identify the modes of transmission of the disease when this particular gene is involved. These results can be found in Nature Communications.

First described in 1952 at the University of Geneva (UNIGE) by the ophthalmologist Maurice Goldenhar (1924-2001), Goldenhar syndrome or oculo-auriculo-vertebral dysplasia is a rare congenital disorder with facial asymmetry, malformations of the auditory and ocular systems, and spinal column anomalies, sometimes associated with mental retardation. It varies greatly in expression and severity depending on the individual and is thought to affect approximately one in 3,500 to 5,600 births.

This syndrome is caused by mutations that appear during foetal development. Do these mutations occur spontaneously or is there an inherited form of the disease? The mode of transmission and the molecular mechanisms involved are still poorly understood. A recent international research effort, led by a joint team from the UNIGE and Beihang University, in China, is providing new elements for understanding the disease. The scientists have identified a gene -- FOXI3 -- whose pathogenic variants are involved in one form of the disease.

Breaking a longstanding impasse in our understanding of olfaction, scientists at UC San Francisco (UCSF) have created the first molecular-level, 3D picture of how an odor molecule activates a human odorant receptor, a crucial step in deciphering the sense of smell.

The findings, appearing online March 15, 2023, in the journal Nature, are poised to reignite interest in the science of smell with implications for fragrances, food science, and beyond. Odorant receptors -- proteins that bind odor molecules on the surface of olfactory cells -- make up half of the largest, most diverse family of receptors in our bodies; A deeper understanding of them paves the way for new insights about a range of biological processes.

"This has been a huge goal in the field for some time," said Aashish Manglik, MD, PhD, an associate professor of pharmaceutical chemistry and a senior author of the study. The dream, he said, is to map the interactions of thousands of scent molecules with hundreds of odorant receptors, so that a chemist could design a molecule and predict what it would smell like.

"But we haven't been able to make this map because, without a picture, we don't know how odor molecules react with their corresponding odor receptors," Manglik said.

New research shows that people with extreme look-alike faces share common genotypes, but differ in their DNA methylation and microbiome landscapes.

“For decades, the existence of individuals who resemble each other without having any family ties has been described as a proven fact, but only in anecdotal terms and without any scientific justification,” said senior author Dr. Manel Esteller, a researcher at the Josep Carreras Leukaemia Research Institute. “The widespread use of the Internet and social networks for image-sharing has meant that we are now able to identify and study such people.”

In their study, Dr. Esteller and his colleagues set out to characterize a set of look-alike humans on a molecular level. To do so, they recruited human doubles from the photographic work of François Brunelle, a Canadian artist who has been obtaining worldwide pictures of look-alikes since 1999. They obtained headshot pictures of 32 look-alike pairs. They determined an objective measure of likeness for the pairs using three different facial recognition algorithms. In addition, the participants completed a comprehensive biometric and lifestyle questionnaire and provided saliva DNA for multiomics analysis. “This unique set of samples has allowed us to study how genomics, epigenomics, and microbiomics can contribute to human resemblance,” Dr. Esteller said.

Overall, the results revealed that these individuals share similar genotypes, but differ in their DNA methylation and microbiome landscapes. Half of the look-alike pairs were clustered together by all three algorithms. Genetic analysis revealed that 9 of these 16 pairs clustered together, based on 19,277 common single-nucleotide polymorphisms. Moreover, physical traits such as weight and height, as well as behavioral traits such as smoking and education, were correlated in look-alike pairs.

Taken together, the results suggest that shared genetic variation not only relates to similar physical appearance, but may also influence common habits and behavior. “Our findings provide a molecular basis for future applications in fields such as biomedicine, evolution, and forensics,” Dr. Esteller said. “It would be very interesting to follow up the potential application in forensics, using the genome of unknown people to prepare bioinformatic strategies to reconstruct the face from DNA. And in medicine, we may be able to deduce the genome of a person from facial analysis and hence use this as a pre-screening tool to detect the presence of genetic mutations associated with disease and apply preventive strategies at an early stage. Some previous studies have compared the genome of individuals with face traits, but in the general population,” he added.

Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, scientists now generated a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. They were able to comprehensively characterize the heterogeneity of cells in tissues and to identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. They also identified several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-β, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia.

This important work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.

Scientists have developed a powerful, inclusive new tool for genomic research that boosts efforts to develop more precise treatments for many diseases by leveraging a better representation of the genetic diversity of people around the world.

The new tool will allow researchers to compare natural variations in our genes against genome sequences collected from a diverse group of people. Until now, scientists have compared these variations with a "reference genome" primarily sequenced from a few volunteers (~70% from one person) living near laboratories involved in the Human Genome Project almost 20 years ago. This represented genomes from a small number of people in a small number of countries.

The new software tool, called "Giraffe," enables the use of a reference point that is far more diverse and inclusive. Instead of relying on a single reference genome, Giraffe uses a "pangenome" that incorporates information about genome sequences from people around the world. This will give scientists a much more global perspective and help them understand why diseases often strike certain groups disproportionately.

"A major advantage of Giraffe is that it enables fast and sensitive comparison of short-read human genome sequences to a pangenome, which is essential for the widespread use of reference graphs that reduce bias in the human genome reference," said researcher Stephen S. Rich, PhD, of the University of Virginia School of Medicine's Center for Public Health Genomics. "Since the current effort in genomics is to move from a European-Caucasian base to a global representation, Giraffe can better define genetic variation in non-white populations and, as a result, have a major impact on precision medicine and application to understanding the genetic risk of disease."

Modern genetic evidence suggests that statue builders on islands such as Rapa Nui, also known as Easter Island, had a shared ancestry.

Polynesian voyagers settled islands across a vast expanse of the Pacific Ocean within about 500 years, leaving a genetic trail of the routes that the travelers took, scientists say. Comparisons of present-day Polynesians’ DNA indicate that sea journeys launched from Samoa in western Polynesia headed south and then east, reaching Rarotonga in the Cook Islands by around the year 830. From the mid-1100s to the mid-1300s, people who had traveled farther east to a string of small islands called the Tuamotus fanned out to settle Rapa Nui, also known as Easter Island, and several other islands separated by thousands of kilometers on Polynesia’s eastern edge. On each of those islands, the Tuamotu travelers built massive stone statues like the ones Easter Island is famed for.

That’s the scenario sketched out in a new study in the Sept. 23 2021 Nature by Stanford University computational biologist Alexander Ioannidis, population geneticist Andrés Moreno-Estrada of the National Laboratory of Genomics for Biodiversity in Irapuato, Mexico, and their colleagues. The new analysis generally aligns with archaeological estimates of human migrations across eastern Polynesia from roughly 900 to 1250. And the study offers an unprecedented look at settlement pathways that zigged and zagged over a distance of more than 5,000 kilometers, the researchers say.

Want to swim with the fishes? New research unravels what makes fish fins so strong yet flexible at the same time.

Fish fins do not contain muscles, yet fish can change their shape with high precision and speed to produce large and complex hydrodynamic forces—a combination of high morphing efficiency and high flexural stiffness that is rare in modern morphing and robotic materials. These “flexo-morphing” capabilities are rare in modern morphing and robotic materials of human design. The thin rays that stiffen the fins and transmit actuation include mineral segments, a prominent feature whose mechanics and function are not fully understood. 

Now, a group of scientists and engineers use mechanical modeling and mechanical testing on 3D-printed ray models to show that the function of the segmentation is to provide combinations of high flexural stiffness and high morphing amplitude that are critical to the performance of the fins and would not be possible with rays made of a continuous material.

Fish fin–inspired designs that combine very soft materials and very stiff segments can provide robotic materials with large morphing amplitudes and strong grasping forces.

A team led by researchers from the Broad Institute of MIT and Harvard, the National Institutes of Health, and Vanderbilt University Medical Center has used base editing, a recently developed form of gene editing, to rescue disease symptoms and lifespan in mice that have Hutchinson-Gilford progeria syndrome.

Progeria is a progressive genetic disorder in humans that leads to death, typically from cardiovascular failure, by the time most patients reach their mid-teens. The majority of children with this disorder have a single-letter change in their DNA that causes the production of a toxic protein.

In a recent study, mice engineered to carry the progeria mutation, and demonstrating nearly all features of the human disease, received a single injection with a base editor programmed to correct the disease-causing mutation. These mice retained healthy tissues and lived two and a half times as long as control mice with progeria that were injected with saline. Indeed, the treated mice reached an age that corresponds to the beginnings of old age in healthy mice.

The study is one of the first examples of using base editing — a gene editing technique that directly converts an individual DNA base pair into a different base pair — inside an animal to rescue a serious genetic disease.